The performance of the peripheral vascular bed depends on the coordinated behavior of several types of microvascular elements which are under the control of neural, humoral, and local mechanisms. The objective of this research program is to develop a quantitative description of the behavior of the various microvascular elements during local regulation of blood flow, by direct observation of the microcirculation and to determine what processes and events are responsible for the coordination of flow and metabolism. We are investigating this problem by observing the microcirculation, which permits precise descriptive studies on the nature of microvascular responses and assessment of which vessel types are involved. Delivery of oxygen to the cells will be assessed by measuring hemoglobin oxygenation in individual microvessels and determining how cellular oxygen supplies are regulated at the microvessel level. We propose to determine both in vitro and in vivo reactivity of microvascular elements to substances related to local control. Results of microvessel reactivity determinations will be evaluated in the light of findings obtained by measuring concentrations of oxygen, potassium, adenosine, and perhaps other vasoactive substances in the environment of the arteriolar smooth muscle. We also propose to determine how concentrations change during regulation of blood flow. Three types of local blood flow regulation will be studied: functional hyperemia in striated muscle, reactive hyperemia in striated muscle and epithelial tissue, and the response to increases and decreases in suffusion solution PO2.